Outcome Prediction for Estrogen Receptor-Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics

Background Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor-positive (ER+) breast cancer. Methods Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. Results Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). Conclusions Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherap

Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics

BACKGROUND: Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor–positive (ER+) breast cancer. METHODS: Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer–specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. RESULTS: Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). CONCLUSIONS: Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherapy

Clinical and microbiological evaluation of an extended-wear hearing instrument

This study aimed to examine the integrity of the ear canal skin and its microbiological changes caused by an extended-wear hearing device. An extended-wear hearing device, Lyric2 (Phonak AG, Switzerland), which is the second generation of the Lyric device, was fitted to 52 ears of 27 subjects. A refit of the device was done for a selection of ears (n = 15) for which the initial fitting was interrupted (28 ears). A matching control group consisted of 10 ears of 10 subjects with no history of using any form of hearing aid for 3 months. The ear canal skin of ears fitted with the hearing device was inspected using an otoendoscope, and signs of problematic pathological conditions were graded. Microbiological examinations were performed at three different stages following fitting. Wearing the device was interrupted in 28 (53.8%) out of the 52 ears for the initial fitting, and 17 of the 28 interrupted cases (60.7%) were due to issues of the ear canal skin. In 3 of 15 ears (25%) following a refitting, wearing the device was interrupted yet again, and 1 of these 3 interruptions was caused by ear canal skin pathologies. Growth of bacteria was not enhanced or prompted by wearing the Lyric2, and Gram-negative bacteria could not be cultured while the device was in place. Based on aspects of ear canal skin pathology, continuous and nonproblematic uses of the Lyric2 device are presumed to be obtained if the fitting is done carefully. Wearing of the Lyric2 device can be considered safe from a microbiological perspective and does not promote growth of Gram-negative bacteria

Prognostic impact of polypharmacy and drug interactions in patients with advanced cancer.

The risk of potential drug-drug interactions (PDI) is poorly studied in oncology. We included 105 patients with advanced non-small-cell lung cancer (NSCLC), 100 patients with advanced breast cancer (BC) and 100 patients of the palliative care unit (PCU) receiving systemic palliative treatment between 2010 and 2015. All patients suffered from advanced incurable cancer and received basic palliative care. PDI were assessed using the hospINDEX of all drugs approved in Switzerland in combination with a specific drug interaction software. Primary study objective was to assess the prognostic impact of PDI per patient cohort using Kaplan-Meier statistics. The median number of comedications was 5 (range 0-15). Major-risk PDI were detected in 74 patients (24.3%). The number of comedications was significantly associated with PDI (p  11 comedications. Median overall survival (OS) was 8.6 months in NSCLC, 33 months in BC and 1.2 months in PCU patients. PDI were significantly associated with inferior OS in BC (HR = 1.32, 95% CI 1.01-1.74, p = 0.049), but not in NSCLC (HR = 1.11, 95% CI 0.84-1.47, p = 0.45) or PCU (HR = 1.12, 95% CI 0.86-1.45, p = 0.41). PDI remained significantly associated with OS in BC (HR = 1.32, p = 0.049) in the adjusted model. In conclusion, PDI are frequent in patients with advanced cancer and increased caution with polypharmacy is warranted when treating such patients